A target discovery pipeline identified ILT3 as a target for immunotherapy of multiple myeloma

被引：17

作者：

Di Meo, Francesco ^{[1
,2
]}

Iyer, Anjushree ^{[3
]}

Akama, Keith ^{[3
]}

Cheng, Rujin ^{[3
]}

Yu, Christina ^{[1
]}

Cesarano, Annamaria ^{[1
,2
]}

Kurihara, Noriyoshi ^{[1
]}

Tenshin, Hirofumi ^{[1
]}

Aljoufi, Arafat ^{[4
]}

Marino, Silvia ^{[1
]}

Soni, Rajesh K. ^{[5
]}

Roda, Julie ^{[3
]}

Sissons, James ^{[3
]}

Vu, Ly P. ^{[6
]}

Guzman, Monica ^{[7
]}

Huang, Kun ^{[1
]}

Laskowski, Tamara ^{[8
]}

Broxmeyer, Hal E. ^{[4
]}

Roodman, David G. ^{[1
]}

Perna, Fabiana ^{[1
,2
,4
]}

机构：

[1] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA

[2] H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplant & Cellular Immunoth, Tampa, FL 33612 USA

[3] NGM Biopharmaceut, San Francisco, CA USA

[4] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA

[5] Columbia Univ, Herbert Irving Comprehens Canc Ctr, Prote & Macromol Crystallog Shared Resource, Irving Med Ctr, New York, NY USA

[6] British Columbia Canc Ctr, Vancouver, BC, Canada

[7] Weill Cornell Med Coll, New York, NY USA

[8] Lonza Personalized Med, Basel, Switzerland

来源：

CELL REPORTS MEDICINE | 2023年 / 4卷 / 07期

关键词：

CELLS;

D O I：

10.1016/j.xcrm.2023.101110

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Multiple myeloma (MM) is an incurable malignancy of plasma cells. To identify targets for MM immuno-therapy, we develop an integrated pipeline based on mass spectrometry analysis of seven MM cell lines and RNA sequencing (RNA-seq) from 900+ patients. Starting from 4,000+ candidates, we identify the most highly expressed cell surface proteins. We annotate candidate protein expression in many healthy tissues and validate the expression of promising targets in 30+ patient samples with relapsed/refractory MM, as well as in primary healthy hematopoietic stem cells and T cells by flow cytometry. Six candidates (ILT3, SEMA4A, CCR1, LRRC8D, FCRL3, IL12RB1) and B cell maturation antigen (BCMA) present the most favor-able profile in malignant and healthy cells. We develop a bispecific T cell engager targeting ILT3 that shows potent killing effects in vitro and decreased tumor burden and prolonged mice survival in vivo, suggesting therapeutic relevance. Our study uncovers MM-associated antigens that hold great promise for immune -based therapies of MM.

引用

页数：17

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